Objective: Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. Design: Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. Methods: A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. Results: Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. Conclusions: A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

Background: Congenital hepatic hemangiomas (CHHs) are typically considered rapidly involuting tumors, similar to their cutaneous counterparts (RICHs). However, non-involuting tumors remain poorly characterized. This study examines the evolutionary patterns and management strategies for non-involuting congenital hepatic hemangiomas (NICHHs). Methods: We conducted a retrospective review of clinical, imaging, histological, and genetic data of children diagnosed with NICHH—defined as showing no signs of involution for at least 18 months—between 1991 and 2022. Results: Seven patients (five females, two males) were identified. The median age at diagnosis was 42 days (range: 0–1440). Five patients had asymptomatic lesions, predominantly located in the right hepatic lobe. Histologic confirmation was available in three cases, and a GNAQ gene mutation was identified in one. The median follow-up period was 75 months (range: 35–191). Three patients with giant NICHH were treated with sirolimus, resulting in partial response in two cases and lesion stabilization in one. The four untreated patients showed diverse evolutionary patterns, including delayed involution and tardive growth. Conclusions: NICHH lesions demonstrate distinct long-term evolution. Accurate diagnosis and regular monitoring are essential to avoid unnecessary interventions. Sirolimus may offer a promising non-surgical treatment for select patients, particularly those with giant lesions.